Fumarate Hydratase–deficient Renal Cell Carcinoma Is Strongly Correlated With Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome

@article{Trpkov2016FumarateHR,
  title={Fumarate Hydratase–deficient Renal Cell Carcinoma Is Strongly Correlated With Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome},
  author={K. Trpkov and O. Hes and A. Agaimy and M. Bonert and P. Mart{\'i}nek and C. Magi-Galluzzi and G. Kristiansen and Christine L{\"u}ders and G. Nesi and E. Comp{\'e}rat and M. Sibony and D. Berney and R. Mehra and F. Brimo and A. Hartmann and A. Husain and N. Frizzell and K. Hills and F. MacLean and B. Srinivasan and A. Gill},
  journal={The American Journal of Surgical Pathology},
  year={2016},
  volume={40},
  pages={865–875}
}
Hereditary leiomyomatosis and renal cell carcinoma syndrome–associated renal cell carcinomas (RCC) are difficult to diagnose prospectively. We used immunohistochemistry (IHC) to identify fumarate hydratase (FH)-deficient tumors (defined as FH negative, 2-succinocysteine [2SC] positive) in cases diagnosed as “unclassified RCC, high grade or with papillary pattern,” or “papillary RCC type 2,” from multiple institutions. A total of 124 tumors (from 118 patients) were evaluated by IHC for FH and… Expand
A Clinicopathologic and Molecular Analysis of Fumarate Hydratase-deficient Renal Cell Carcinoma in 32 Patients
TLDR
The overall findings show that FH-deficient RCC is considerably heterogenous in morphology and frequently behaves aggressively, and Suspicion for this entity should be raised even in the absence of predominantly papillary architecture and characteristic nucleolar features. Expand
Fumarate hydratase deficient renal cell carcinoma and fumarate hydratase deficient-like renal cell carcinoma: Morphologic comparative study of 23 genetically tested cases.
TLDR
It is evident that neither morphologic feature nor immunohistochemical analysis can be reliably used in routine practice for the diagnosis of HLRCC/FHRCC. Expand
Pattern multiplicity and fumarate hydratase (FH)/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration
Hereditary leiomyomatosis and renal cell carcinoma syndrome is characterized by an increased risk of agressive renal cell carcinoma, often of type 2 papillary histology, and is caused by FH germlineExpand
Fumarate hydratase deficient renal cell carcinoma: Chromosomal numerical aberration analysis of 12 cases.
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Copy number variation pattern in FHRCC/HLRCC appears to be highly variable and does not provide a useful diagnostic tool in identifying these cases. Expand
Comprehensive Molecular Characterization and Response to Therapy in Fumarate Hydratase–Deficient Renal Cell Carcinoma
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Although most FH-RCC tumors are due to germline FH alterations, a significant portion result from biallelic somatic FH loss, combination mTOR/VEGF therapy showed encouraging results. Expand
Fumaratehydratase-deficient renal cell carcinoma: a clinicopathological and molecular study of 13 cases
TLDR
A morphological subtype of FH-deficient RCC with low-grade nuclei and eosinophilic cytoplasm, which might mainly occur in young women and show a relatively good prognosis is observed, which is a rare renal tumour and has a wide morphological spectrum. Expand
Fumarate hydratase-deficient renal cell carcinoma: A clinicopathological study of seven cases including hereditary and sporadic forms.
TLDR
TFE immunoreactivity may occur in some FH-deficient RCCs, and immunohistochemistry can accurately diagnose these tumors and mutational analysis of FH gene, which includes hereditary and sporadic forms. Expand
Tubulocystic Carcinoma of the Kidney With Poorly Differentiated Foci: A Frequent Morphologic Pattern of Fumarate Hydratase-deficient Renal Cell Carcinoma
TLDR
It is concluded that RCCs with TC-PD morphology are enriched for FH deficiency, and the term “FH-deficient RCC” is proposed as a provisional term for tumors with a combination of suggestive morphology and immunophenotype but where genetic confirmation is unavailable upon diagnosis. Expand
Immunohistochemical Characterization of Fumarate Hydratase (FH) and Succinate Dehydrogenase (SDH) in Cutaneous Leiomyomas for Detection of Familial Cancer Syndromes
TLDR
Loss of FH immunohistochemical expression in cutaneous leiomyomas is a sensitive and specific marker for detection of HLRCC, thus suggesting a role for prospective FH IHC in patients with these tumors to screen for H LRCC. Expand
Incidence of Succinate Dehydrogenase and Fumarate Hydratase-Deficient Renal Cell Carcinoma Based on Immunohistochemical Screening with SDHA/SDHB and FH/2SC.
TLDR
Results can help guide immunohistochemistry-based screening strategies for these tumors and lead to a genetic predisposition to hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated RCC. Expand
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TLDR
Although IHC screening for FH may have a role in confirming patients at high risk for hereditary disease before genetic testing, prospective identification of FH-deficient leiomyomas is of limited clinical benefit in screening unselected patients because of the relatively high incidence of somatic mutations. Expand
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TLDR
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TLDR
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TLDR
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